research methodology - target discovery
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Chapter - IV Methodology
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Chapter IV
METHODOLOGY
. .
4.1 Overall Approach
In this present research pursuit, a web-based application (tool) was
developed using Java to predict drug targets from bacterial genome. Using
this web based application, targets were predicted and validated from 80
pathogenic microbes. The targets obtained were organized in a web based
database which will facilitate next steps in drug discovery process. The
application was tested using the genome data of muti-drug resistant
Mycobacterium tuberculosis and the obtained drug targets were critically
analyzed using bioinformatics tools and databases.
4.2 WEB-BASED APPLICATION
Algorithm for target prediction
An algorithm was designed based on the strategic approach derived
to identify potential drug targets and validate them. The algorithm has three
main steps:
1. Prediction of essential genes,
2. Exclusion of human homologs, and
3. Comparison with the existing drug targets.
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Step-1: Prediction of Essential genes
Fig. 4: Algorithm for prediction of essential genes
The DEG was manually downloaded from http://tubic.tju.edu.cn/deg/
and compiled as a database for comparison using the BLAST program
against input sequences. The essential genes in the input pathogenic
microbe are identified in Step-1. The resultant sequences (essential genes
of the microbe) is used as an input sequence for the next step.
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Step-2: Exclusion of human homologs
Fig. 5
Algorithm for predicting targets non homologous with Homo sapiens
The predicted essential genes of the pathogenic microbe are
compared against Homo sapiens. The protein sequences for Homo sapiens
were downloaded from NCBI site (ftp://ftp.ncbi.nlm.nih.gov/genomes/
H_sapiens/protein/) and compared using the BLASTall program. The
sequences which are not matching with the Homo sapiens are retrieved as
a separate text file. This set of sequences will become the input file for the
next step (i.e. target validation).
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Step-3: Comparison with existing drug targets
Fig.6: Algorithm for validating the predicted targets
The third step involves comparison of the essential genes from
the microbe which is not matching with the Homo sapiens are compared
with the approved/proposed targets from Drug Bank. The gene/protein
sequences of approved and proposed targets from Drug Bank is
downloaded (http://redpoll.pharmacy.ualberta.ca/drugbank/) and used for
the comparison.
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At each step the comparison was carried out by integrating
the BLASTall exe. To compare the sequences, BLAST executable from
NCBI (ftp://ftp.ncbi.nlm.nih.gov/blast/executables/) were downloaded and
customized.
The algorithm compares the input genome data with the essential
genes and thereafter with the human genes to exclude the homologs based
on the e-value cutoffs. Then these exclusive sequences from microbial
genome which is not matching with the human homologs are compared with
the approved and proposed targets from Drug Bank to validate them.
The web-based application was developed using JSP (View),
Servlets (Control) and Struts (Framework). Essential BLAST parameters
(-p, -i, -e, and -d) were customized to produce the desired results.
4.2.1 BLAST Parameters
BLAST - Basic Local Alignment Search Tool
Table-3 BLAST Parameters -p
Parameter -p
Function Specifies the type of search
Default None
Input format String
Example To instructs blastall to run blastn program, use: -p blastn
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Table-4 BLAST Parameters -d
Parameter -d
Function Specifies the target database(s)
Default Nr
Input format String
Example To search database named est_human, use: -d est_human
Note: Use database file name WITHOUT the file extension. Even though
multiple databases can be specified in command line, using -d "nr est",
database alias file is a better way to call multiple databases. For more
information on database aliases, see: ftp://ftp.ncbi.nlm.nih.gov/blast/
documents/formatdb.html.
Search multiple large databases together may encounter memory
related problems.
Table-5 BLAST Parameters -i
Parameter -i
Function Specifies input query file
Default None
Input format String
Example To search query file my_query.txt, use: -i my_query.txt
Note: Use the complete file name WITH its extension. The query must be
in FASTA format. If multiple entries are in the input file, all queries will be
searched. To use stdin (default), omit the -i and redirect the file using '<',
like in blastall -pblastp -d refseq_protein <my_aa_query
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Table-6 BLAST Parameters -e
Parameter -e
Function Specifies Expectation value cutoff
Default 10
Input format Real
Example To specify an e-value cutoff of 2 10^-20, use: -e 2e-20
Note: Accepted formats are integer (100), fraction (1/500), decimal (0.005),
and exponential (5e-5). This parameter controls the search sensitivity. To
see less significant hits, increase the setting. Relaxed settings will
decrease the search speed.
The application takes the input (genome of microorganisms) in.ffn or
.txt file format and provides target sequences (potential drug targets) as a
single text file. The input genome sequences should contain all the
sequences in fasta format in a single text file.
4.3 SELECTED PATHOGENIC MICROBES
Data mining and web search was carried out to list all the pathogenic
microbes. Based on prevalence and severity, 80 pathogenic
microorganisms (Annexure-I) were selected for this present research work.
The genome of these 80 pathogenic microbes were downloaded from NCBI
ftpsite (ftp://ftp.ncbi.nlm.nih.gov/genomes/Bacteria). These sequence data
were stored locally for data analysis. The targets obtained from these 80
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organisms were analyzed for their gene name, protein encodes, function,
and pathway for further validation. These analyses were carried out
manually using BLAST program and pathway search in KEGG database.
4.4 COMPREHENSIVE DATA ANALYSIS
From these 80 pathogenic microbes, multi-drug resistant strain
(Mycobacterium tuberculosis) was selected for critical analysis. The targets
obtained from the pathogenic organism were compared with the existing
and proposed targets (Drug Bank) to explore new targets for drug
discovery. Also the targets were analyzed for its conservity among other
pathogens for its narrow or broad spectrum ranges bioinformatics tools.
4.5 WEB-BASED DATABASE
The targets obtained from the rest of the pathogenic microbes were
organized in a web based database to serve as a data resource for drug
discovery. The various fields in the database includes the organism name,
gene name, gene sequence, protein product, pathway, Enzyme Commision
Number (EC No.) and its function. The following figure shows the schema
used of the database.
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Fig. 7: List of database fields and its description
Based on these data types, a web-based database containing
potential and validated drug targets were developed using JSP (frontend)
and MySQL (Backend). The database has the following fields as shown in
Fig.7 and the data can be searched using organism name, gene or protein
name either singly or in combination. AJAX concepts are applied to
database search options to fasten the query search process. The data in
the database can be updated manually or as a single upload from the
spreadsheet. The spreadsheet with following template directly uploads the
data to the web based database.
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4.6 TOOLS AND DATA RESOURCES
4.6.1 Servlet
Servlet is a server side program and web application, Servlet take
the request from client and processes it and gives the response. Java
Servlet has security, session management and instance persistence.
A servlet is a Java programming language class used to extend the
capabilities of servers that host applications accessed via a request-
response programming model. Although servlets can respond to any type of
request, they are commonly used to extend the applications hosted by Web
servers. For such applications, Java Servlet technology defines HTTP-
specific servlet classes.
The javax.servlet and javax.servlet.http packages provide interfaces
and classes for writing servlets. All servlets must implement the servlet
interface, which defines life-cycle methods.
When implementing a generic service, you can use or extend the
Generic servlet class provided with the Java Servlet API. The HttpServlet
class provides methods, such as doGet and doPost, for handling HTTP-
specific services.
4.6.2 JSP
JavaServer Pages technology put snippets of servlet code directly
into a text-based document. A JSP page is a text-based document that
contains two types of text: static template data, which can be expressed in
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any text-based format such as HTML, WML, and XML, and JSP elements,
which determine how the page constructs dynamic content.
JavaServer Pages (JSP) technology enables Web developers and
designers to rapidly develop and easily maintain, information-rich, dynamic
Web pages that leverage existing business systems. As part of the Java
technology family, JSP technology enables rapid development of Web-
based applications that are platform independent. JSP technology
separates the user interface from content generation, enabling designers to
change the overall page layout without altering the underlying dynamic
content.
The JavaServer PagesTM (JSP) technology provides a simplified, fast
way to create web pages that display dynamically generated content. JSP
technology was designed to make it easier and faster to build web-based
applications that work with a wide variety of web servers, application
servers, browsers and development tools.
The JSP Approach to Web Application Development
In developing the JSP specification, Sun Microsystems worked with a
number of leading web server, application server and development tool
vendors, as well as a diverse and experienced development community.
The result is an approach that balances portability with ease-of-use for
application and page developers.
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JSP technology speeds the development of dynamic web pages in a
number of ways
Separating content generation from presentation
Using JSP technology, web page developers use HTML or XML tags
to design and format the results page. They use JSP tags or scriptlets to
generate the dynamic content (the content that changes according to the
request, such as requested account information or the price of a specific
bottle of wine). The logic that generates the content is encapsulated in tags
and JavaBeans components and tied together in scriptlets, all of which are
executed on the server side. If the core logic is encapsulated in tags and
beans, then other individuals, such as web masters and page designers
can edit the JSP page without affecting the generation of the content.
On the server, a JSP engine interprets JSP tags and scriptlets,
generates content (for example, by accessing JavaBeans components,
accessing a database with JDBCTM technology, or including files), and
sends the results back in the form of an HTML (or XML) page to the
browser. This helps authors protect proprietary code while ensuring
complete portability for any HTML-based web browser.
Emphasizing Reusable Components
Most JSP pages rely on reusable, cross-platform components
(JavaBeans or Enterprise JavaBeansTM components) to perform the more
complex processing required of the application. Developers can share and
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exchange components that perform common operations, or make them
available to larger user or customer communities. The component-based
approach speeds overall development and lets organizations leverage their
existing expertise and development efforts for optimal results.
Simplifying Page Development with tags
Web page developers are not always programmers familiar with
scripting languages. The JavaServer Pages technology encapsulates much
of the functionality required for dynamic content generation in easy-to-use,
JSP-specific XML tags. Standard JSP tags can access and instantiate
JavaBeans components, set or retrieve bean attributes, download applets,
and perform other functions that are otherwise more difficult and time-
consuming to code.
The JSP Page Components
A JSP directive passes information to the JSP engine. In this case,
the first line indicates the location of some Java programming language
extensions to be accessible from this page. Directives are enclosed in
<%@ and %> markers.
Fixed template data: Any tags that the JSP engine does not
recognize it passes on with the results page. Typically, these will be HTML
or XML tags. This includes the Unordered List and H1 tags in the example
above.
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JSP actions, or tags: These are typically implemented as standard
tags or customized tags, and have XML tag syntax.
An expression: The JSP engine evaluates anything between <%==
and %> markers. A scriptlet is a small script that performs functions not
supported by tags or ties everything together. The native scripting language
for JSP 1.0 software is based on the Java programming language.
JSP Directives
JSP pages use JSP directives to pass instructions to the JSP engine.
These may include the following:
JSP Page Directives communicate page-specific information, such as
buffer and thread information or error handling.
Language Directives specify the scripting language, along with any
extensions.
The Include Directive (shown in the example above) can be used to
include an external document in the page. A good example is a copyright
file or company information, file -- it is easier to maintain this file in one
central location and include it in several pages than to update it in each
JSP page. However, the included file can also be another JSP file.
A taglib Directive indicates a library of custom tags that the page can
invoke.
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JSP Tags
Most JSP processing will be implemented through JSP-specific XML-
based tags. JSP 1.0 includes a number of standard tags, referred to as the
core tags. These include:
jsp:useBean This tag declares the usage of an instance of a JavaBeans
component. If the Bean does not already exist, then the JavaBean
component instantiates and registers the tag.
jsp:setProperty This sets the value of a property in a Bean.
jsp:getProperty This tag gets the value of a Bean instance property,
converts it to a string, and puts it in the implicit object "out".
jsp:include
jsp:forward
The 1.1 releases will include additional standard tags. The advantage
of tags is that they are easy to use and share between applications. The
real power of a tag-based syntax comes with the development of custom
tag libraries, in which tool vendors or others can create and distribute tags
for specific purposes.
Scripting Elements
JSP pages can includes include small scripts, called scriptlets, in a
page. A scriplet is a code fragment, executed at request time processing.
Scriptlets may be combined with static elements on the page (as in the
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example above) to create a dynamically generated page. Scripts are
delineated within <% and %> markers. The scripting language engine will
evaluate anything within those markers. The JSP specification supports all
of the usual script elements, including expressions and declarations.
Application Models for JSP Pages
A JSP page is executed by a JSP engine, which is installed in a web
server or a JSP-enabled application server. The JSP engine receives
requests from a client to a JSP page, and generates responses from the
JSP page to the client. JSP pages are typically compiled into Java Servlets.
Java Servlets are a standard Java extension, described in more detail at
www.java.sun.com. The page developer has access to the complete Java
application environment, with all of the scalability and portability of the Java
technology-enabled family. When a JSP page is first called, if it does not
yet exist, it is compiled into a Java Servlet class and stored in the server
memory. This enables very fast responses for subsequent calls to that
page. (This avoids the CGI-bin problem of spawning new processes for
each HTTP request, or the runtime parsing required by server-side
includes.)
JSP pages may be included in a number of different application
architectures or models. JSP pages may be used in combination with
different protocols, components and formats. The following sections
describe a few of the possibilities.
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The Future for JSP Technology
JSP technology is designed to be an open, extensible standard for
building dynamic web pages. Developers will use JSP pages to create
portable web applications that can run with different web and application
servers for different markets, using whatever authoring tools fit their market
and their needs. By working with a consortium of industry leaders, Sun has
ensured that the JSP specification is open and portable. You should be
able to author JSP pages anywhere and deploy them anywhere, using any
client and server platforms. Over time, tool vendors and others will extend
the functionality of the platform by providing customized tag libraries for
specialized functions.
Java Script
JavaScript may be considered a derivative of the programming
language Java. But while both are tools for providing interactivity into web
pages, they are as different as bananas and papayas. Java is a complex
programming environment where you create packaged ("compiled")
software applications that you can insert into a web page. The learning
curve for Java is monumental at best (despite claims of the expanding
number of software tools). On the other hand, JavaScript offers a simpler
set of programming instructions that you can enter directly among the
HTML formatting of your web pages, and code that can be easily accessed
and modified.
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Before JavaScript, to create interactive forms (web pages with fields,
buttons, and menus) we needed to write computer programs ("CGI" scripts)
that resided on and ran from a web server. But with JavaScript, you can
perform many form tasks without connecting to a web server. In the jargon,
we are processing on the "client-side".
Even better, JavaScript allows you to create content that is dynamic,
so that the code inside one web page can produce many different types of
displays and features depending on the viewer's actions, including the
images that change when you move the mouse over a graphic.
JavaScript combined with the absolute screen positioning available in
web browsers that support HTML 4.0 provide what is known as Dynamic
HTML, or DHTML.
Advantages of JavaScript
As stated above, JavaScript provides interactivity for your web pages
without relying on server-side "CGI" (Common Gateway Interface)
programming, which means your pages can be interactive even when you
are not connected to the Internet. Since the code is typed directly into your
HTML files, you can create Javascript with software as simple as a plain
text editor. You can quickly test and modify JavaScript code. JavaScript
functionality is built into most newer web browsers since 1996, so there is
no extra software for the viewer to download or install.
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JavaScript also provides useful commands for testing the viewer’s
capability to view other types of web multimedia (i.e. whether they have
Shockwave installed). Although not all web browsers may support
JavaScript, there are fairly reliable methods for you to direct viewers to
alternative pages.
Because of its wide use, there are numerous reference sites for
learning about JavaScript as well as many sites to download free code that
you can use. We'll share a few with you in the next section.
Disadvantages of JavaScript
If you lack experience in programming, JavaScript will look daunting
to you. Often, it is not clear how the code works when you examine the
HTML source. Long, complicated JavaScript can add quite a bit of
download time to your HTML page.
Although JavaScript is supported on the two major web browsers,
there are a few differences that may cause problems. Many of the graphic
HTML creation tools do not handle JavaScript very well.
4.7 MICROSOFT SQL SERVER
4.7.1 Relational Database Concepts
Databases contain data that's specifically organized. A database can
be as simple as a flat file (a single computer file with data usually in a
tabular form) containing names and telephone numbers of one's friends, or
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as elaborate as the worldwide reservation system of a major airline. During
the 90s, the relational data access scheme came to the forefront.
Relational scheme views data as rows of information.
Each row contains columns of data, called fields. The main concept in
the relational scheme is that the data is uniform. Each row contains the
same number of columns. One such collection of rows and columns is
called a table. Many such tables form a relational database. Tables contain
records. There are three types of data record relationships between
records:
1. One-to-one. One record in a table is related to at least one record in
another table.
2. One-to-many relationship. One record in a table could be associated
with many records in another table.
3. Many-to-many relationships. Many records in a table could be
associated with many records in another table.
4.7.2 Features of RDBMS
A relational DBMS must be able to manage databases entirely through
its relational capabilities. All information in a relational database
(including table and column names) is represented explicitly as values
in tables.
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Guaranteed access: Every value in a relational database is guaranteed
to be accessible by using a combination of the table name, primary key
value, and column name.
Systematic null value support: The DBMS provides systematic support
for the treatment of null values (unknown or inapplicable data), distinct
from default values, and independent of any domain.
Active, online relational catalog: The description of the database and
its contents is represented at the logical level as tables and can
therefore be queried using the database language. View updating--All
views that are theoretically updateable can be updated through the
system.
Set-level insertion, update, and deletion: The DBMS supports not only
set-level retrievals but also set-level inserts, updates, and deletes.
Physical data independence: Application programs and ad hoc
programs are logically unaffected when physical access methods or
storage structures are altered.
Logical data independence: Application programs and ad hoc programs
are logically unaffected, to the extent possible, when changes are
made to the table structures.
Integrity independence: The database language must be capable of
defining integrity rules. They must be stored in the online catalog, and
they cannot be bypassed.
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Distribution independence: Application programs and ad hoc requests
are logically unaffected when data is first distributed or when it is
redistributed.
No subversion: It must not be possible to bypass the integrity rules
defined through the database language by using lower-level
languages.
This method has several advantages and many disadvantages. In its
favor is the fact that the physical structure of data on a disk becomes
unimportant. The programmer simply stores pointers to the next
location, so data can be accessed in this manner. Also, data can be
added and deleted easily. However, different groups of information
could not be easily joined to form new information. The format of the
data on the disk could not be arbitrarily changed after the database
was created. Doing so would require the creation of a new database
structure.
4.7.3 Microsoft SQL Server
Microsoft SQL Server is a relational database management system
produced by Microsoft. It supports Microsoft's version of Structured Query
Language (SQL), the most common database language. It is commonly
used by businesses for small- to medium-sized databases, and - in the past
five years - some large enterprise databases.
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Brief History of SQL Server
The code base for Microsoft SQL Server (prior to version 7.0)
originated in Sybase SQL Server, and was Microsoft's entry to the
enterprise-level database market, competing against Oracle, IBM, and
Sybase. Microsoft, Sybase and Ashton-Tate teamed up to create and
market the first version named SQL Server 4.2 for OS/2 (about 1989) which
was essentially the same as Sybase SQL Server 4.0 on Unix, VMS, etc.
Microsoft SQL Server for NT v4.2 was shipped around 1992 (available
bundled with Microsoft OS/2 version 1.3) and was a simple port from OS/2
to NT. Microsoft SQL Server v6.0 was the first version of SQL Server that
was architect for NT and did not include any direction from Sybase.
About the time Windows NT was coming out, Sybase and Microsoft
parted ways and pursued their own design and marketing schemes.
Microsoft negotiated exclusive rights to all versions of SQL Server written
for Microsoft operating systems. Later, Sybase changed the name of its
product to Adaptive Server Enterprise to avoid confusion with Microsoft
SQL Server. Until 1994 Microsoft's SQL Server carried three Sybase
copyright notices as an indication of its origin.
Several revisions have been done independently since with
improvements for SQL Server. SQL Server 7.0 was the first true GUI based
database server and was a rewrite away from the legacy Sybase code, a
variant of SQL Server 2000 was the first commercial database for the Intel
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IA64 architecture. During this time there was a rivalry between Microsoft
and Oracle's servers for winning the market over enterprise customers.
The current version, Microsoft SQL Server 2005, was released in
November of 2005. The launch took place alongside Visual Studio 2005
and BizTalk Server 2006. The SQL Server 2005 Express edition is currently
available for free download. The Microsoft SQL Server product is not just a
database, it also contains (as part of the product) an enterprise ETL tool
(Integration Services), Reporting Server, OLAP and messaging
technologies specifically Service Broker.
Versions for Windows
1993 - SQL Server 4.21 for Windows NT
1995 - SQL Server 6.0, codenamed SQL95
1996 - SQL Server 6.5, codenamed Hydra
1999 - SQL Server 7.0, codenamed Sphinx
1999 - SQL Server 7.0 OLAP, codenamed Plato
2000 - SQL Server 2000 32-bit, codenamed Shiloh
2003 - SQL Server 2000 64-bit, codenamed Liberty
2005 - SQL Server 2005, codenamed Yukon
Next release - codenamed Katmai
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Description
MS SQL Server uses a variant of SQL called T-SQL, or Transact-
SQL, an implementation of SQL-92 (the ISO standard for SQL, certified in
1992) with some extensions. T-SQL mainly adds additional syntax for use
in stored procedures, and affects the syntax of transactions support. (Note
that SQL standards require (ACID) Atomic, Consistent, and Isolated,
Durable transactions.) MS SQL Server and Sybase/ASE both communicate
over networks using an application-level protocol called Tabular Data
Stream (TDS). The TDS protocol has also been implemented by the
FreeTDS project ((1)) in order to allow more kinds of client applications to
communicate with MS SQL Server and Sybase databases. MS SQL Server
also supports Open Database Connectivity (ODBC).
Variants
A stripped-down version of Microsoft SQL Server known as MSDE
(Microsoft SQL Server Desktop Engine) is distributed with products such as
Visual Studio, Visual FoxPro, Microsoft Access, ASP.NET Web Matrix, and
other products. MSDE has some restrictions: a limit of 2 GB databases, and
it comes with no GUI tools to administer it. It also has a workload governor,
which reduces its speed once you exceed 8 concurrent workloads on the
engine.
Microsoft recently released the successor to MSDE, dubbed SQL
Server Express. Similar to MSDE, SQL Express includes all the core
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functionality of SQL Server and the workload governor was removed, but
places restrictions on the scale of databases. It will only utilize a single
CPU, 1 GB of RAM, and imposes a maximum size of 4 GB per database
(log sizes don't count). Microsoft provides a separate download ("feature
pack") for the Express edition that includes less feature rich version of
Reporting Services. SQL Express also doesn't include enterprise features
such as Analysis Services, Data Transformation Services, and Notification
Services. Unlike MSDE, SQL Express includes a management console,
called SQL Server Management Studio Express.
4.8 JAVA DATABASE CONNECTIVITY (JDBC)
The Java Database Connectivity (JDBC) of the Java Enterprise APIs
is the first of such cross-platform, cross-database approaches to database
access from Java programs. The Enterprise APIs also consist have Remote
Method Invocation (RMI) and serialization APIs (for Java programs to
Marshall objects across namespaces and invoke methods in remote
objects), Java IDL (Interface Definition Language) for communicating with
CORBA, and other object-oriented systems. The JDBC APIs and the JDBC-
ODBC Bridge, you can access and interact effectively with almost all
databases from Java applets and applications.
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4.8.1 JDBC Drivers
JDBC Drivers are set of classes that enable the Java application to
communicate with databases. Java.sql that ships with JDK contains various
classes for using relational databases. But these classes do not provide
any implementation only the behaviors are defined. The actual
implementations are done in third-party drivers. Third party vendors
implement the java.sql.Driver interface in their database driver.
JDBC technology drivers fit into one of four categories:
1. A JDBC-ODBC bridge provides JDBC API access via one or more
ODBC drivers. Note that some ODBC native code and in many cases
native database client code must be loaded on each client machine
that uses this type of driver. Hence, this kind of driver is generally
most appropriate when automatic installation and downloading of a
Java technology application is not important. For information on the
JDBC-ODBC Bridge driver provided by Sun.
2. A native-API partly Java technology-enabled driver converts JDBC
calls into calls on the client API for Oracle, Sybase, Informix, DB2, or
other DBMS. Note that, like the bridge driver, this style of driver
requires that some binary code be loaded on each client machine.
3. A net-protocol fully Java technology-enabled driver translates JDBC
API calls into a DBMS-independent net protocol which is then
translated to a DBMS protocol by a server. This net server middleware
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is able to connect all of its Java technology-based clients to many
different databases. The specific protocol used depends on the
vendor. In general, this is the most f lexible JDBC API alternative. It is
likely that all vendors of this solution will provide products suitable for
Intranet use. In order for these products to also support Internet
access they must handle the additional requirements for security,
access through firewalls, etc., that the Web imposes. Several vendors
are adding JDBC technology-based drivers to their existing database
middleware products.
4. A native-protocol fully Java technology-enabled driver converts JDBC
technology calls into the network protocol used by DBMSs directly.
This allows a direct call from the client machine to the DBMS server
and is a practical solution for Intranet access. Since many of these
protocols are proprietary the database vendors themselves will be the
primary source for this style of driver. Several database vendors have
these in progress.
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